Autoantibodies in Systemic Sclerosis

https://doi.org/10.1016/j.semarthrit.2005.03.005Get rights and content

Objectives

To describe the clinical, laboratory, and prognostic features associated with the scleroderma-specific autoantibodies.

Methods

Using the Pittsburgh Scleroderma Databank, all consecutive patients seen between 1980 and 1995 who had autoantibody studies performed were studied. Anticentromere antibodies (ACA), antitopoisomerase (TOPO), anti-U1-RNP (U1-RNP), anti-RNA Polymerase III (Pol 3), anti-U3-RNP (U3-RNP), anti-Th/To (Th/To), and anti-Pm/Scl (Pm/Scl) were determined according to previously described methods. The frequency of clinical features, organ system outcomes, and survival within the patients with a specific antibody were cumulative over the course of the disease. The frequency of a specific feature was compared across groups to identify significant manifestations and outcomes in patients with a specific antibody.

Results

Some demographic, clinical, and organ system findings were associated with the specific antibody, and other features with the scleroderma subtype (limited cutaneous or diffuse cutaneous scleroderma). U3-RNP, U1-RNP, and TOPO were seen more commonly in African-American patients, and ACA was seen in older, female Caucasians. Muscle inflammation was seen in patients with U1-RNP and U3-RNP. Digital tip ulcers and digital tuft resorption were seen more frequently in those with ACA and TOPO. A vasculopathy causing pulmonary hypertension typically occurs with ACA and pulmonary fibrosis with TOPO; however, both types of lung disease were seen in patients with nucleolar antibodies, Th/To and U3-RNP. Importantly, severe interstitial fibrosis was rarely seen in cases with Pol 3. Renal crisis was strongly associated with Pol 3. Survival within limited scleroderma was decreased in the Th/To patients compared with ACA patients. Within the diffuse scleroderma group, patients with Pol 3 had the best survival.

Conclusions

Scleroderma autoantibodies are associated with very specific demographic, clinical, organ system, and survival features.

Relevance

The determination of scleroderma autoantibodies may be helpful in assessing the prognosis, monitoring, and treatment of scleroderma patients.

Section snippets

Methods

Scleroderma patients from the Pittsburgh Scleroderma Databank whose initial visit was between July 1, 1980 and July 1, 1995 are included in this study. All patients had a standardized baseline evaluation (3) and are followed every 1 to 2 years as part of the Pittsburgh Scleroderma Outcome Study. As of 2000, 93% of these patients were accounted for. Deaths were confirmed through the Social Security Death Index and causes of death were determined from information obtained from our records, the

Results

There were 1432 patients who had autoantibody assays performed during the above time period: Of these, 291 patients had ACA, 318 had TOPO, 71 had U1-RNP, 120 had Pol 3, 55 had U3-RNP, 72 had Th/To, and 36 had Pm/Scl. Table 1 summarizes the demographic features in these patients. Only 8% of ACA patients were male compared with 19 to 26% in the other groups (P < 0.01). Only 3% of ACA, 4% of Th/To, and 4% of Pol 3 patients were African-Americans compared with 32% of U3-RNP, 17% of TOPO, and 13% of

Discussion

Autoantibodies have been associated with systemic sclerosis since the 1960s when they were first identified (14). The observation that the ACA and TOPO antibodies were closely related to the classical manifestations of the 2 major subsets of scleroderma, limited (CREST syndrome) and diffuse scleroderma, led to a better understanding of these distinct clinical subsets (5, 10, 15). Since then, at least 7 scleroderma-specific antibodies have been identified, each with unique clinical associations.

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    Supported by the Arthritis Foundation Clinical Science Award.

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